July 17, 2000 Washington DC -- The reason that jet lag hits some travelers hard and barely fazes others may lie in our mothers' genes, suggests a report in the 14 July issue of international journal, Science.
A French study on circadian clocks, which regulate the body's daily cycles, has found that female zebrafish "set" the clocks of their young before birth. Variations in certain maternal genes may therefore affect how easily the body's time-keeping system adjusts to changes in the day/night cycle.
Until now, scientists have generally assumed that the circadian clock doesn't start working until around the time of birth, or possibly later. Now, scientists from Ecole Normale Supérieure, CNRS, and the Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ Université Louis Pasteur have found that a key component of the circadian clock starts "ticking" in zebrafish eggs even before they are fertilized. The gene's activity keeps the same rhythm as the animal develops.
"These findings were quite a surprise. The current belief is that circadian rhythms need a developed brain, so they don't get started until later," said Vincent Laudet, a coauthor of the Science paper along with Franck Delaunay, Christine Thisse, Oriane Marchand, and Bernard Thisse.
Researchers are seeking ways to help our clocks reset themselves in response to a trans-Atlantic flight, for example, or a night-time workshift. Disrupted clocks have also been associated with sleep disorders and affective disorders such as depression. Understanding how the clock is set in the first place could be an important step toward treating these ailments.
The genes that run the circadian clock aren't fully understood yet, but their activity seems to follow a self-sustained loop synchronized by light. When a clock gene is switched on, it directs the cell to produce proteins, which eventually trigger a signal that switches the gene off. The process comes full circle when conditions change again, turning the gene back on.
Working together, the clock genes create so-called circadian rhythms in the body, which help control the timing of a variety of biological changes, including hormone production, blood pressure, and the metabolism's slowdown during sleep.
The Period, or "Per," gene is one of the most important clock genes known in fruit flies and mammals. Laudet and his colleagues identified a version of this gene, Per3, in zebrafish and found that the gene's activity rose and fell at a steady pace in both unfertilized and fertilized eggs-regardless of when fertilization took place.
In fact, the researchers observed this pattern in the fertilized egg, or "zygote," before the zygote had begun expressing its own genes. (Until a certain point, the zygote relies on a supply of genetic information left in the egg.)
"The embryos know exactly what time it is even thought their clocks aren't working independently," Laudet said.
He and his colleagues knew, therefore, that the zebrafish embryos must have inherited the "ticking" Per3 directly from their mothers.
The scientists suspect that this process may happen in mammals too. The team studied zebrafish because their genetics are relatively well-understood and the young develop separately from the mother. Mammals are more difficult to study because mothers pass various substances to their fetuses, which could influence the fetal circadian clock.
The next step is to find out how just how much of the circadian clock is inherited in assembled form. Laudet and his colleagues did find another gene, for example, that doesn't seem to participate in the circadian cycle until later in development.
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